Brain injury continues to be a major cause of death and disability throughout the world. Our investigations of hyperbaric oxygen treatment (HBOT) indicate that it is a relatively safe treatment that has promise as a potential therapy for patients with severe traumatic brain injury (TBI) Our initial prospective clinical trial to assess the effectiveness of HBOT in severe TBI documented significant improvement in survival, particularly in certain subgroups of patients In our second study, HBOT was found to improve cerebral aerobic metabolism in patients with severe TBI, reduce elevated intracranial pressure, and had a persistent positive effect for at least six hours following the treatment Our work suggests that HBOT may allow the brain to utilize baseline amounts of oxygen more efficiently following treatment This is an important finding in that HBOT can be delivered intermittently as needed to maintain its positive effect Recently, increasing the inspired oxygen concentration to 100% (FiO2 enhancement) has been proposed as a way of delivering supranormal levels of oxygen to severe TBI patients FiO2 enhancement also improves cerebral aerobic metabolism as measured by decreased lactate and increased brain tissue oxygen levels in the brain during treatment The relative ease of FiO2 enhancement administration and its inexpense require that it be compared to HBOT The goals of the present proposal are to further elucidate the mechanisms of action of HBOT on severe TBI and to test hypotheses that are crucial to the possible future design of a Phase Ii1 clinical trial This will be accomplished with a prospective, randomized, unblinded clinical trial comparing HBO at two durations (30 minutes versus 60 minutes), FiO2 enhancement, and standard therapy in a control group of severely brain-injured patients This study is designed to compare the effect of HBOT and FiO: enhancement on various cerebral metabolic parameters as well as ICP Continuous monitoring of the effect of oxygen treatment on cerebral aerobic metabolism over a 24-hour period will give us a better understanding of the mechanisms of action of supranormal oxygen on the brain Potential oxygen toxicity on the brain and lungs also will be evaluated As consistently noted by the reviewers of our grant, our center and personnel are uniquely qualified to perform these goals